Neonates have increased susceptibility to infection, which leads to increased mortality. Whether or not this as a result of implicit deficits in neonatal innate immune function or recapitulation of innate immune effector cell populations following infection is unknown. Here, we examine the process of emergency myelopoiesis whereby the host repopulates peripheral myeloid cells lost following the initial infectious insult. As early inflammatory responses are often dependent upon NF-?B and type I IFN signaling, we also examined whether the absence of MyD88, TRIF or MyD88 and TRIF signaling altered the myelopoietic response in neonates to polymicrobial sepsis. Following neonatal polymicrobial septic challenge, hematopoietic stem cell (HSC) expansion in bone marrow and the spleen were both attenuated and delayed in neonates compared with adults. Similar reductions in other precursors were observed in neonates. Similar to adult studies, the expansion of progenitor stem cell populations was also seen in the absence of MyD88 and/or TRIF signaling. Overall, neonates have impaired emergency myelopoiesis in response to sepsis compared with young adults. Despite reports that this expansion may be related to TLR signaling, our data suggest that other factors may be important, as TRIF(-/-) and MyD88(-/-) neonatal HSCs are still able to expand in response to polymicrobial neonatal sepsis.
Ogilvie's syndrome is a rare and potentially fatal disease that can easily be mistaken for postoperative ileus. Also known as acute colonic pseudo-obstruction, early recognition and diagnosis of the syndrome allows for treatment prior to bowel perforation and requisite abdominal surgery. The authors report a case of Ogilvie's syndrome following spinal deformity correction and tethered cord release in an adolescent who presented with acute abdominal distension, nausea, and vomiting on postoperative Day 0. The patient was initially diagnosed with adynamic ileus and treated conservatively with bowel rest, reduction in narcotic dosage, and a regimen of stool softeners, laxatives, and enemas. Despite this treatment, her clinical course failed to improve, and she demonstrated significant colonic distension radiographically. Intravenous neostigmine was administered as a bolus with a rapid and dramatic response. This case is the first reported instance of neostigmine use for Ogilvie's syndrome treatment following a pediatric neurosurgical operation.
Populations encompassing extremes of age, including neonates and elderly, have greater mortality from sepsis. We propose that the increased mortality observed in the neonatal and elderly populations after sepsis is due to fundamental differences in host-protective immunity and is manifested at the level of the leukocyte transcriptome. Neonatal (5-7 d), young adult (6-12 wk), or elderly (20-24 mo) mice underwent a cecal slurry model of intra-abdominal sepsis. Both neonatal and elderly mice exhibited significantly greater mortality to sepsis (p < 0.05). Neonates in particular exhibited significant attenuation of their inflammatory response (p < 0.05), as well as reductions in cell recruitment and reactive oxygen species production (both p < 0.05), all of which could be confirmed at the level of the leukocyte transcriptome. In contrast, elderly mice were also more susceptible to abdominal peritonitis, but this was associated with no significant differences in the magnitude of the inflammatory response, reduced bacterial killing (p < 0.05), reduced early myeloid cell activation (p < 0.05), and a persistent inflammatory response that failed to resolve. Interestingly, elderly mice expressed a persistent inflammatory and immunosuppressive response at the level of the leukocyte transcriptome, with failure to return to baseline by 3 d. This study reveals that neonatal and elderly mice have profoundly different responses to sepsis that are manifested at the level of their circulating leukocyte transcriptome, although the net result of increased mortality is similar. Considering these differences are fundamental aspects of the genomic response to sepsis, interventional therapies will require individualization based on the age of the population.
Congenital diaphragmatic hernia (CDH) is a frequently lethal birth defect and, despite advances, extracorporeal life support (ie, extracorporeal membrane oxygenation [ECMO]) is commonly required for severely affected patients. Published data suggest that CDH survival after 2 weeks on ECMO is poor. Many centers limit duration of ECMO support.
Most agents used for GA are considered to be neurotoxins and affect developing brains in experimental models, leading to a push for spinal anesthesia (SA). There are no reports of laparoscopic pyloromyotomy (LP) performed under SA. We present our experience with LP and SA and discuss feasibility.
The bluntnose sixgill shark, Hexanchus griseus, is a widely distributed but poorly understood large, apex predator. Anecdotal reports of diver-shark encounters in the late 1990's and early 2000's in the Pacific Northwest stimulated interest in the normally deep-dwelling shark and its presence in the shallow waters of Puget Sound. Analysis of underwater video documenting sharks at the Seattle Aquarium's sixgill research site in Elliott Bay and mark-resight techniques were used to answer research questions about abundance and seasonality. Seasonal changes in relative abundance in Puget Sound from 2003-2005 are reported here. At the Seattle Aquarium study site, 45 sixgills were tagged with modified Floy visual marker tags, along with an estimated 197 observations of untagged sharks plus 31 returning tagged sharks, for a total of 273 sixgill observations recorded. A mark-resight statistical model based on analysis of underwater video estimated a range of abundance from a high of 98 sharks seen in July of 2004 to a low of 32 sharks seen in March of 2004. Both analyses found sixgills significantly more abundant in the summer months at the Seattle Aquarium's research station.
To assess the impact of varying approaches to congenital diaphragmatic hernia (CDH) repair timing on survival and need for ECMO when controlled for anatomic and physiologic disease severity in a large consecutive series of patients with CDH.
Conditions for a catalytic asymmetric aza-Darzens aziridine synthesis mediated by a vaulted biphenanthrol (VAPOL) magnesium phosphate salt is described. Using simple substrates, this methodology explores the scope and reactivity of a new magnesium catalyst for an aziridination reaction capable of building chirality and complexity simultaneously.
The captive husbandry of giant Pacific octopuses Enteroctopus dofleini is well understood, but their endocrine signatures are not well documented. The major vertebrate reproductive hormones--estrogen, progesterone, and testosterone--and the stress-related hormone corticosterone are relatively well known for many vertebrate species. However, few studies on these hormones within invertebrates have been conducted. Our hypothesis was that endocrine signatures within octopuses are similar to those found within vertebrates in response to reproductive activity and stress. Using standard immunoassay techniques, we measured fecal steroids within fecal samples collected from five female and three male giant Pacific octopuses housed at the Seattle Aquarium. The mean estrogen level ranged from 3.67 to 99.39 ng/g of feces, progesterone ranged from 44.35 to 231.71 ng/g feces, testosterone ranged from 9.30 to 18.18 ng/g feces, and corticosterone ranged from 10.91 to 22.14 ng/g feces. The results suggest that octopus fecal hormones are similar to those in vertebrates and may be useful in measuring ovarian activity and stress within captive female giant Pacific octopuses.
Conditions for the phosphoric acid-catalyzed highly enantioselective ring-opening of meso-aziridines with a series of functionalized aromatic thiol nucleophiles are described. The procedure utilizes commercially available aromatic thiols, a series of meso-aziridines, and a catalytic amount of VAPOL phosphoric acid to explore the substrate scope of this highly enantioselective reaction.
Carcinoid syndrome, characterized by flushing, diarrhea, and valvular heart disease, can occur following carcinoid tumor metastasis to the liver and systemic release of bioactive hormones into the systemic circulation. Treatment of this devastating disease is hampered by the lack of an in vivo model that recapitulates the clinical syndrome.
Novel sixgill shark (Hexanchus griseus) microsatellite loci were developed and tested on five shark species. A suite of microsatellite loci previously developed for lemon sharks (Negaprion brevirostris) was also tested. Data on 15 microsatellites are presented including primer sequences, number of alleles (a), observed (H(O) ) and expected heterozygosities (H(E) ), and F(IS) values for sixgill sharks (a = 10-69, H(O) = 0.24-1.00, H(E) = 0.76-0.96 and F(IS) = -0.21-0.60), sevengill sharks (Notorynchus cepedianus) (a = 6-40, H(O) = 0.20-0.73, H(E) = 0.59-0.94 and F(IS) = -0.47-0.58), Pacific spiny dogfish (Squalus acanthias) (a = 3-13, H(O) = 0.00-0.96, H(E) = 0.24-0.93 and F(IS) =-0.52-1.00), angle sharks (Squatina californica) (a = 1-4, H(O) = 0.00-1.00, H(E) = 0.60-1.00 and F(IS) =-1.00-0.25), and leopard sharks (Triakis semifasciata) (a = 3-16, H(O) = 0.20-1.00, H(E) = 0.53-0.92 and F(IS) = -0.57-1.00). A final suite of 14 microsatellites (13 developed from sixgill sharks and one from lemon sharks) were found to be polymorphic and conform to Hardy-Weinberg equilibrium within sixgill sharks.
All existing sea otter, Enhydra lutris, populations have suffered at least one historic population bottleneck stemming from the fur trade extirpations of the eighteenth and nineteenth centuries. We examined genetic variation, gene flow, and population structure at five microsatellite loci in samples from five pre-fur trade populations throughout the sea otters historical range: California, Oregon, Washington, Alaska, and Russia. We then compared those values to genetic diversity and population structure found within five modern sea otter populations throughout their current range: California, Prince William Sound, Amchitka Island, Southeast Alaska and Washington. We found twice the genetic diversity in the pre-fur trade populations when compared to modern sea otters, a level of diversity that was similar to levels that are found in other mammal populations that have not experienced population bottlenecks. Even with the significant loss in genetic diversity modern sea otters have retained historical structure. There was greater gene flow before extirpation than that found among modern sea otter populations but the difference was not statistically significant. The most dramatic effect of pre fur trade population extirpation was the loss of genetic diversity. For long term conservation of these populations increasing gene flow and the maintenance of remnant genetic diversity should be encouraged.
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